Algos Therapeutics, Inc., a biopharmaceutical company, seeks funding for early drug discovery research designed to validate two proprietary ion channels as molecular targets for treatment of neuropathic pain. Neuropathic pain is initiated by nerve damage and appears to involve excessive electrical activity in sensory neurons and inappropriate inflammation of peripheral receptive fields. Patients with diabetes, cancer, arthritis, multiple sclerosis, and viral infections (herpes) are at risk for neuropathic pain. Few effective therapies for this type of chronic pain are now available. This Phase I SBIR proposal encompasses research that will determine where these targets are located both throughout the body and specifically in pain pathways. This will be done through measurment of mRNA encoding our targets and detection of the target proteins using immunocytochemistry and Western blot technology. The targets will be further validated using animal models of neuropathic pain. The normal function of the targets will be blocked by administration of antisense oligonucleotides to the intrathecal space. This treatment will reduce the amount of the targets expressed in the pain pathways and thereby reduce their normal function. Behavioral measures of allodynia and thermal hyperalgesia will be used to evaluate the analgesia generated by antisense treatment. Preliminary data suggests that our targets are involved in pain signaling and demonstrates our technical capabilities as well as the feasibility of our strategy. The goal of this Phase I project is to determine which of our two targets represents the most biologically important choke point of pain perception. The Phase II proposal will involve later stage drug discovery research such as assay development, lead seeking, and lead optimization. The immediate goal of this project is to produce a compound directed at our most attractive molecular target that is ready for human clinical testing. The long-term goal of our work is to develop an effective and safe treatment for neuropathic pain.